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You star in the ABC drama "Black-ish", which follows an African-American family who struggles to find their sense of cultural identity within a mainly white, middle class neighborhood. Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease. Because NAFLD resembles alcoholic liver disease but occurs in people who drink little or no alcohol, excessive daily alcohol consumption must be ruled out before making the diagnosis.
Accurate epidemiologic data are not available because of a lack of population-based studies and reliable noninvasive screening tools.
Based on the available data, NAFLD is estimated to occur in one-third of the general population in the US.
Overall, morbidity and mortality have been shown to be significantly higher in NASH patients compared with the general population. Further studies are needed to define the pathogenesis of NAFLD clearly and explain the apparent inter-individual variation in the susceptibility to progress to more-advanced liver disease. Most persons with NAFLD are asymptomatic, and liver disease is often discovered incidentally when laboratory examination shows elevated liver enzyme levels. NAFLD is usually diagnosed during further evaluation for elevated aminotransferase levels found in one of three situations: on routine checkup, when monitoring is performed for possible side effects of drugs (most often cholesterol-lowering medication), or for nonspecific symptoms. Primary noninvasive evaluation may be used to confirm the diagnosis of fatty liver disease, given the risks and costs of a liver biopsy. In a patient with suspected NAFLD or NASH, useful baseline testing should include levels of AST, ALT, total and direct bilirubin, and fasting serum glucose, as well as a lipid panel. Liver biopsy is of unquestioned value in determining the presence of steatosis, distinguishing steatosis from steatohepatitis, and assessing the degree of fibrosis.
NAFLD is histologically indistinguishable from liver damage resulting from alcohol-induced liver injury.
Despite the advantages of liver biopsy, its overall role in the evaluation of patients with NAFLD is unsettled, in large measure because of its risks and poor patient acceptance. Because of the important limitations of the currently available noninvasive and invasive tests, recent efforts have focused on identifying potential novel noninvasive biomarkers for NASH and assessment of fibrosis. The goal of treatment is to improve steatosis and prevent the development of fibrosis, which can lead to cirrhosis and its complications. Weight reduction has been widely studied in adults with NASH and has been shown to improve not only the biochemical results but also the histology. Peroxisome proliferator-activated receptor gamma (PPARg) agonists (thioglitazones) have been shown to improve insulin resistance, a surrogate marker of fatty liver, and histology by promoting redistribution of triglycerides from the liver and muscle into proliferating adipocytes.
Oxidative stress has been hypothesized to contribute to the progression of NAFLD to NASH and to worsen insulin resistance.
In a randomized controlled trial, L-carnitine was found to improve steatosis, NAFLD histologic activity score and aminotransferases. Emerging data from recent trials have suggested that weight loss through lifestyle modifications, as well as several insulin-sensitizing, antioxidants, hepatoprotective medications and others, may be of benefit in patients with NAFLD (Table 3). Vitamin E is considered a first-line therapy in biopsy proven NASH in the practice guidelines although it is not advised in patients with diabetes or cirrhosis. In patients with decompensated NAFLD cirrhosis, liver transplantation should be considered. More than 50 million Americans have been estimated to have the metabolic syndrome, and 80% of them probably have NAFLD. Nonalcoholic fatty liver disease (NAFLD), a condition associated with obesity and diabetes, is increasingly being recognized in the Western population. The diagnosis is often made after an incidental finding of elevated liver enzyme levels or due to the clinician’s suspicion regarding a patient with obesity or diabetes. NAFLD affects a substantial portion of the general population and is associated with metabolic syndrome, which includes obesity, insulin resistance, hyperlipidemia, and hypertension. Williams CD, Stengel J, Asike MI et al: Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy. Della Corte C, Alisi A, Iorio R et al: Expert opinion on current therapies for nonalcoholic fatty liver disease. Sanyal AJ, Chalasani MB, Kowdley KV et al: Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. Musso G, Gambino R, Cassader M, Paganu G: A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease.
Loria P, Adinolfi LE, Bellentani S et al: Practice guidelines for the diagnosis and management of nonalcoholic fatty disease.
Until now, the only defense against cervical cancers caused by HPV has been the annual Pap smear—a test that will show if there are abnormal cells on a woman’s cervix.
Gardasil is a recently approved HPV vaccine that prevents infections with HPV types 6, 11, 16, and 18. There are approximately six million people in the United States each year who develop a genital HPV infection, but most of these infections will disappear within a year or two without treatment. Detection: The HPV infections most likely to cause precancerous and cancerous changes in the mucosal cells are difficult to detect because they do not cause symptoms. Genital Warts: Although both men and women can develop genital warts, the HPV viruses that cause these warts are considered to be at low risk of progression to precancerous and cancerous tumors. Women should continue to have annual Pap smears to look for precancerous changes in the cervix, even if they have received the new HPV vaccine. There is almost nothing that can cause a false positive pregnancy test, and all of the causes require an urgent visit to a health care provider. Numerous other conditions leading to fatty liver must be excluded by history, physical examination, and appropriate testing (Table 1). There is disagreement about the methods used to diagnose NASH, and there is no clear consensus on the clinical implications of histologic changes or on the influence of the amount of alcohol ingested. The prevalence is increased in men, older individuals (those aged 40-70 years), and those with components of the metabolic syndrome especially diabetes and abdominal obesity. With the initial insult, macrovesicular steatosis occurs which is a manifestation of excessive triglyceride accumulation in the liver. Coronary artery disease and malignancy followed by liver-related mortality are the most common causes of death in NASH patients.
Genetic factors have been suggested to play an important role in this variation, and several new candidate genes have been proposed.
It is the most common cause of unexplained persistent elevation of liver enzyme levels after hepatitis and other chronic liver diseases have been excluded. NAFLD can also be identified incidentally on imaging or, less often, on liver biopsy done for other reasons.
Fatty infiltration of the liver produces a diffuse increase in echogenicity (a bright liver) and vascular blurring (Figure 2).
Because the diagnostic accuracy of noninvasive diagnostic tools is low, histology is the most reliable means to grade the severity of the disease and thus estimate prognosis.
In patients with risk factors for NAFLD (ie, metabolic syndrome), 3 to 6 months are often allowed for a trial of weight loss and for possible improvements in imaging studies and biochemical markers of liver disease.
Because the prognosis of NASH depends on risk factors (eg, obesity, insulin resistance, type 2 diabetes), these conditions have been the focus of treatment. A review of 3 randomized controlled trials on weight reduction through lifestyle and pharmacologic intervention suggested that weight loss is safe and can improve histologic parameters of NASH. Several drugs have been studied, including sibutramine, a serotonin reuptake inhibitor, and orlistat, which reduces fat absorption. Reports have demonstrated improvement in transaminase levels with different classes of drugs, but there is a lack of histologic follow-up.
For this reason, antioxidant treatment to reduce this stress and slow the progression of the disease has been studied. Despite small adult studies suggesting a role of ursodeoxycholic acid in the improvement of NASH, a large, randomized, placebo-controlled trial has demonstrated no benefits from ursodeoxycholic acid over placebo on liver biochemistry and histology.
Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers (ARBs) can improve insulin sensitivity. Pilot studies based on the theory that NAFLD may be linked to small bowel bacterial overgrowth have shown some promise with the use of probiotics and prebiotics.
In 2010, the Italian Association for the Study of the Liver and in 2012 the American Association for the Study of Liver Diseases in conjunction with the American College of Gastroenterology and the American Gastroenterological Association published evidence-based practice guidelines for the diagnosis and management of NAFLD. Pioglitazone can be used to treat steatohepatitis in biopsy-proven NASH but long-term safety has not been established and it’s use in a NASH population with diabetes has not been studied. Coexisting conditions (eg, morbid obesity, severe complications of diabetes, cardiac disease) and fear of intraoperative and post-transplantation complications, may preclude transplantation candidacy in these patients.


Furthermore, about one-third of the US population suffering from type 2 diabetes mellitus has fatty liver.
Patients with NAFLD not only frequently suffer from insulin resistance but also have increased overall mortality. Papillomaviruses are called such because they can cause certain kinds of warts, or papillomas, on skin and mucous membranes in different areas of the body. Most often, these infections go away without treatment in patients who have normal immune systems. Annual Pap smears allow the doctor to identify cell changes far in advance of the development of cervical cancer. This vaccine must be given before HPV develops, so it is recommended for girls and women before they become sexually active (ages 9 to 26 years). Sometimes, an HPV infection of the cervix will linger for a longer period of time and may (or may not) lead to precancerous changes in the mucosal tissue cells of the cervix. In women, an annual Pap smear can detect cervical cell changes considered to be precancerous, but for men, there is no similar test available to detect early-stage, HPV-related cancers such as anal cancer. However, to avoid spreading HPV, genital warts that are apparent should be treated before continuing sexual activity.
The risk of sexually transmitted HPV infections can be somewhat reduced by using a condom, but condoms are not 100% effective, since they do not cover the entire genital area. The only time your get a positive is when HCG is in your urine and your pregnant.Menopause is not a hormone.
It ranges from steatosis (simple fatty liver), to nonalcoholic steatohepatitis (NASH–fatty changes with inflammation and hepatocellular injury or fibrosis), to advanced fibrosis and cirrhosis (Figure 1).
The prevalence of NAFLD is affected by many factors, including genetics (predilection to alcohol abuse, sex) and environment and is therefore difficult to define.
It seems to occur in approximately 3% of the US population but may be found in more than 25% of obese persons. Insulin resistance and subsequent hyperinsulinemia appear to lead to alterations in the hepatic pathways of uptake, synthesis, degradation, and secretion of free fatty acids and ultimately to accumulation of lipids in the hepatocytes. Children with NASH also have a significantly shorter duration of survival compared with people in the general population. The most common symptoms that bring NAFLD to medical attention are malaise, fatigue, and right upper quadrant or diffuse abdominal discomfort. Some centers screen for NAFLD in high-risk groups that include patients with elements of the metabolic syndrome.
Generally, the ratio of AST to ALT is <1, but this ratio increases as fibrosis advances.
Unfortunately, ultrasound cannot rule out steatohepatitis or fibrosis, and its sensitivity drops sharply when <30% of hepatocytes contain fat droplets.
Treatment proposed for NAFLD has been based on the 2-insult hypothesis; the first being fatty liver infiltration (linked to obesity and insulin resistance) and the second being oxidative stress. Both of these have been shown to improve liver enzyme levels and sonographic signs of fatty liver. However, the safety of bariatric surgery in patients with cirrhosis is still under investigation. Metformin, a biguanide oral anti-diabetic agent, lowers hepatic glucose production and promotes glucose uptake in the muscles. A recent phase 3, randomized, placebo-controlled, double blind clinical trial on the use of pioglitazone versus vitamin E versus placebo for the treatment of non-diabetic patients with NASH (PIVENS trial) showed no difference in the rate of improvement in NASH compared with placebo but it did show a reduction in aminotransferases and hepatic steatosis.
Several small trials in humans with NAFLD have supported an effect of tocopherol (vitamin E) on the improvement of transaminase levels but there have been discordant results in histologic improvement.
Pentoxifylline inhibits a number of proinflammatory cytokines and may have hepatoprotective effects. ARBs, in small studies including a randomized controlled trial, have shown improvement in histologic inflammation and fibrosis.
An inverse association between coffee consumption and severity of fibrosis has been seen in multiple studies.
A thorough pretransplantation evaluation, as well as better weight and metabolic derangement control, may be necessary. The prevalence of NAFLD in the US seems to be substantially greater than the 2% prevalence of hepatitis C virus infection and is believed to be increasing. Although simple fatty liver seems to be a benign condition, it can progress to NASH and ultimately to cirrhosis in some patients. About one third of HPVs affect the genital areas, including the cervix, vagina, vulva, anus, rectum, penis, and scrotum, and are spread by sexual contact. Scientists have known for some time that certain types of HPV (notably, types 16 and 18) are linked to precancerous changes of the cervix and eventually result in 70% of all cervical cancers.
If a woman has an abnormal Pap smear, a test for HPV can determine if a virus is present and which virus is causing the infection.
Gardasil has been proven very effective in preventing HPV infections from the four types of HPV listed above, but it does not protect a woman against all of the HPV infections that can cause cervical cancer.
HPV infections have also been related to vulvar and vaginal cancers, anal cancer, cancer of the penis, and other cancers of mucosal tissues in the mouth and throat. In men—and women—who have anal sex, anal cancer is becoming more common, and a test similar to the Pap smear is in the early stages of development. Changes in cervical or anal mucosal cells should be closely monitored by a physician to determine the appropriate treatment to avoid future cancers. Better literacy ("you will get a positive," instead of "your get a positive," "won't, instead of "wont," and "you're pregnant," not "your pregnant") as well as a citation to some medical authority would also help to improve this answer.
Studies suggest that although simple fatty liver is a benign condition, NASH can progress to fibrosis and lead to end-stage liver disease. NAFLD has been observed in all ethnic groups with the highest prevalence seen in Hispanics compared with Caucasians and African Americans. These changes seem to make the liver susceptible to a second insult, resulting in an inflammatory response and progression of liver damage. Data suggest that the natural history of NAFLD is determined by the severity of the histologic damage. It is most important to include anti-hepatitis C antibody as well as serum ceruloplasmin levels in young patients.
Liver enzyme levels are normal in a large percentage of patients with NAFLD; normal aminotransaminase levels do not exclude the presence of advanced disease. In addition to establishing the cause and severity of disease, histology permits the monitoring of disease progression and the response to therapy, because aminotransaminase levels can decrease during the course of the disease regardless of whether fibrosis progresses or improves. The spectrum of abnormalities varies from simple bland steatosis to NASH, in which steatosis is associated with mixed inflammatory cell infiltration and liver injury.
A repeat liver biopsy in patients with NASH in 3-5 years should be considered to monitor disease progression.
Reduction of dietary carbohydrates, in particular dietary fructose, is the most beneficial and has been found to improve the lipid profile in overweight patients. A meta-analysis of rimonabant, a cannabinoid-1-antagonist, showed that it is associated with increased adverse events and currently it cannot be recommended for NAFLD. Randomized clinical trials are needed to determine if bariatric surgery is an appropriate therapy in NASH patients.
Longer term trials suggest that long term therapy with thioglitazones are needed to maintain histologic improvement but would offer no additional histologic benefit. Probucol, a lipophilic lipid lowering drug, has shown improvement in aminotransferases but it can also reduce high density lipoprotein levels. One small randomized study showed improvement in histologic features of NASH when compared with placebo. A 3% to 4% loss in body weight likely improves steatosis, and weight of loss up to 10% may improve necro-inflammation.
Statins are deemed safe to use to treat dyslipidemia but are not currently recommended to treat NASH specifically.
Following transplant, most patients have persistent metabolic syndrome, with long-term implications.
Because of the consequences of the disease, we emphasize the importance of the detection of NAFLD in high-risk groups, including obese patients, as well as those with evidence of insulin resistance or other components of metabolic syndrome.
These growths are usually not cancerous, but there are a few HPVs that are positively linked to precancerous growths on the cervix and anal mucosa.
Other HPV types (primarily types 6 and 11) are known to cause 90% of all genital warts in both men and women.


Follow-up Pap smears every four to six months may be recommended to watch for further cell changes.
It is estimated that nearly 500,000 women around the world will be diagnosed with cervical cancer this year; of those, 10,000 cases will affect American women.
At this time, the vaccine is known to provide protection from its target HPV viruses for at least a four-year period. The disease is mostly silent and is often discovered through incidentally elevated liver enzyme levels. Oxidative stress, mainly caused by mitochondrial dysfunction, and proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), are believed to play an important role in the progression of liver damage in NAFLD. Most patients with NAFLD have pure steatosis without inflammation and are reported to have a benign clinical course. When cirrhosis appears, stigmata of chronic liver disease, such as spider angiomata, ascites, splenomegaly, hard liver border, palmar erythema, or asterixis, can be present. Serum alkaline phosphatase and g-glutamyl transpeptidase levels may also be mildly abnormal. Both computed tomography (CT) and magnetic resonance imaging (MRI) studies, especially the new technique of magnetic resonance spectroscopy, are more sensitive modalities for quantifying steatosis. A histologic scoring system (NAFLD activity score) has been proposed to aid with diagnosis and monitoring of the disease.
Cell injury is manifested by hepatocyte ballooning and by Mallory hyaline and acidophil bodies. High- to moderate-intensity exercise (30 minutes, 3 to 5 times a week) has also been advocated to reduce the risk of comorbidities associated with obesity.
Randomized controlled trials have shown improved serum liver enzymes and insulin resistance but inconsistent effects on liver histology.
Hepatotoxicity has been described with thioglitazones, and a more common side effect is paradoxical weight gain and fat redistribution. Although one of the most common side effect of statins is liver enzyme level elevation, evidence has pointed out that patients with elevated baseline transaminase levels (likely having NAFLD) who receive statin treatment do not have a higher incidence of liver enzyme level elevation or hepatotoxicity than liver disease control subjects who do not receive statins. Polyunsaturated fatty acids, studied in 3 randomized controlled trials, have been shown to improve biochemical and ultrasound features of liver steatosis (a phase II trial is underway). Further advances in understanding the pathogenesis of NAFLD, such as induction of toll-like receptors leading to proinflammatory and profibrogenic cytokines which contribute to NASH, may also help to provide new therapeutic options for NASH. Moreover, NAFLD has been shown to recur in the liver allograft, with a possible rapid progression to steatohepatitis and cirrhosis. Basic laboratory evaluation of liver enzyme levels might point to the diagnosis but cannot rule out NAFLD if test results are normal, and imaging techniques have poor sensitivity for low-grade steatosis. Screening and surveillance methods should be applied more uniformly from center to center, and reliable noninvasive techniques are needed to diagnose NAFLD and the detection of progressive liver disease. The discovery of a vaccine that can prevent the vast majority of cervical cancer cases is an exciting step in cancer prevention. Research is being done to determine how long immunity will last and whether a booster shot of the vaccine will be required later in life. It is strongly associated with obesity and insulin resistance and is currently considered by many as the hepatic component of the metabolic syndrome.
Potential oxidative stressors include hepatic iron, leptin, antioxidant deficiencies, and intestinal bacteria. Of patients with NASH 15% to 25% progress to cirrhosis and its complications over 10 to 20 years. Patients might complain of jaundice or pruritus, or they might present with a complication of portal hypertension (eg, ascites, variceal bleeding, or encephalopathy). Given that more than 80% of patients with NAFLD have some components of metabolic syndrome, serum levels of fasting cholesterol and triglycerides, as well as fasting glucose and insulin, should be determined. However, none of these imaging techniques has sufficient sensitivity and specificity for staging the disease and cannot distinguish between simple bland steatosis and NASH with or without fibrosis. However, more realistically, patients should be encouraged to incorporate moderate activity into everyday life (eg, climbing stairs, walking instead of driving).
A large randomized trial in children with NASH did not show a sustained reduction in ALT or improvements in NAFLD activity score for histologic features in the liver.
Although controversial, increased risk of cardiovascular events and bone loss with the use of rosiglitazone as well as of increased risk of heart failure with pioglitazone have been described. Moreover, the clinical relevance of the current recommendation that liver biochemistry should be checked before and periodically (usually 12 weeks) after treatment initiation has not been substantiated in the NAFLD population. Moreover, because these tests do not differentiate simple steatosis from NASH, a liver biopsy must be discussed with the patient if the suspicion of NASH is strong.
Although the vaccine was studied in boys and was found to be safe, it is not yet known whether it will work to prevent genital warts or anal or penile cancers. NASH cirrhosis is now one of the leading indications for liver transplantation in the United States. Hepatocyte apoptosis, an organized form of cell death, has been identified as a potential key component of the second insult involved in NAFLD progression. At the time of initial biopsy, as many as one-third of NASH patients have advanced hepatic fibrosis, whereas 10% to 15% have well-established cirrhosis. Most patients have associated features of the metabolic syndrome (Table 2): obesity (47%-90%), diabetes mellitus (28%-55%), and variable incidences of hyperlipidemia (4%-92%) and hypertension. Albumin, bilirubin, and platelet levels are usually normal unless the disease has evolved to cirrhosis.
Hepatic elastography is a non-invasive measurement of hepatic fibrosis by measuring liver stiffness, which is increased with increased fibrosis.
Bariatric surgery in the appropriate individual may be useful to control obesity but the guidelines indicate that bariatric surgery is not yet an established option for the treatment of NASH. Therefore, although generalized screening for fatty liver in all at-risk patients may be difficult and is not recommended by the practice guidelines, it is certainly warranted to look for and actively manage the metabolic syndrome (obesity, diabetes, hyperlipidemia, and hypertension). Weight loss regimens are believed to be helpful, and numerous drugs have been investigated in small studies.
The HPV vaccine was tested in thousands of people prior to its approval, and it was found to be both safe and effective. It is now recognized that a large portion of patients with cryptogenic cirrhosis have burned-out NASH: the histologic feature of steatosis or steatohepatitis is replaced by a bland cirrhosis. Some patients with NAFLD have low titers of autoimmune antibodies (antinuclear and antia€“smooth muscle antibody) and an elevation of ferritin. Large randomized clinical trials are necessary to determine the real benefit of these agents. Finally, studies on the pathogenesis of NAFLD may not only improve our understanding of the mechanisms involved in NAFLD progression but also may lead to novel therapeutic strategies to treat this condition.
Data in Japanese patients suggest that the cumulative rate of HCC at 5 years may be as high as 15%. Recurrence after liver transplantation has also been reported as has de novo NAFLD following liver transplantation for other reasons. You should time and record the time you perform the test, and read results at the instructed time. Fishing your test out of the garbage after too much time has passed can change the initial results. Some tests allow you to see what can best be described as a watermark; kind of like what you see on US paper currency. If there is no color or you have to really mess with it in the light to see a line; it could be an evaporation line.
Sometimes urine can be contaminated with blood or large amounts of protein, which can lead to false positive results. If you receive a positive result from a home pregnancy test it is important to see your doctor. It's is not common, rare medical conditions can cause false positive results on home pregnancy tests.
If you're unsure about the results of your home pregnancy test, ALWAYS consult your doctor.



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